Mobile Tigecycline Resistance: An Emerging Health Catastrophe Requiring Urgent One Health Global Intervention

Anyanwu, Madubuike Umunna; Nwobi, Obichukwu Chisom; Okpala, Charles Odilichukwu R.; Ezeonu, Ifeoma M.

doi:10.3389/fmicb.2022.808744

Cited by 24 publications

(23 citation statements)

References 128 publications

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“…Tigecycline is structurally related to the tetracycline class of antibiotics and is active against Gram‐positive and Gram‐negative bacteria, as well as tetracycline‐resistant bacteria and some anaerobes (Yaghoubi et al, 2022 ). Resistance mechanisms to tigecycline include non‐mobile tet (X) and mobile‐plasmid‐mediated transmissible tet (X) and resistance‐nodulation‐division (RND) efflux pump mediated tmexCD‐toprJ genes (Anyanwu et al, 2022 ) Of most concern is the transferable plasmid‐mediated spread of tigecycline resistance genes such as tet (X3) and tet (X4), which confer high levels of resistance to all tetracyclines, including tigecycline (MICs of ≥ 32 mg/L). Two recent studies looking at the global distribution, evolution pattern and spread of tet (X) genes, identified isolates carrying tet (X) genes from over 20 countries across five continents (Pan et al, 2020 ; Wang et al, 2021 ).…”

Section: Antimicrobial Resistance In Salmonella Sppmentioning

confidence: 99%

The European Union Summary Report on Antimicrobial Resistance in zoonotic and indicator bacteria from humans, animals and food in 2020/2021

2023

EFS2

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Antimicrobial resistance (AMR) data on zoonotic and indicator bacteria from humans, animals and food are collected annually by the EU Member States (MSs) and reporting countries, jointly analysed by EFSA and ECDC and presented in a yearly EU Summary Report. This report provides an overview of the main findings of the 2020–2021 harmonised AMR monitoring in Salmonella spp., Campylobacter jejuni and C. coli in humans and food‐producing animals (broilers, laying hens and turkeys, fattening pigs and bovines under 1 year of age) and relevant meat thereof. For animals and meat thereof, indicator E. coli data on the occurrence of AMR and presumptive Extended spectrum β‐lactamases (ESBL)‐/AmpC β‐lactamases (AmpC)‐/carbapenemases (CP)‐producers, as well as the occurrence of methicillin‐resistant Staphylococcus aureus are also analysed. In 2021, MSs submitted for the first time AMR data on E. coli isolates from meat sampled at border control posts. Where available, monitoring data from humans, food‐producing animals and meat thereof were combined and compared at the EU level, with emphasis on multidrug resistance, complete susceptibility and combined resistance patterns to selected and critically important antimicrobials, as well as Salmonella and E. coli isolates exhibiting ESBL‐/AmpC‐/carbapenemase phenotypes. Resistance was frequently found to commonly used antimicrobials in Salmonella spp. and Campylobacter isolates from humans and animals. Combined resistance to critically important antimicrobials was mainly observed at low levels except in some Salmonella serotypes and in C. coli in some countries. The reporting of a number of CP‐producing E. coli isolates (harbouring bla OXA‐48 , bla OXA‐181 , and bla NDM‐5 genes) in pigs, bovines and meat thereof by a limited number of MSs (4) in 2021, requests a thorough follow‐up. The temporal trend analyses in both key outcome indicators (rate of complete susceptibility and prevalence of ESBL‐/AmpC‐ producers) showed that encouraging progress have been registered in reducing AMR in food‐producing animals in several EU MSs over the last years.

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Section: Antimicrobial Resistance In Salmonella Sppmentioning

confidence: 99%

The European Union Summary Report on Antimicrobial Resistance in zoonotic and indicator bacteria from humans, animals and food in 2020/2021

2023

EFS2

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“…Current antibiotic therapies are increasingly suffering from limited efficacy due to broadly developing resistances in common pathogenic bacteria. − One of the most challenging objectives in modern drug discovery is therefore the continuous development of novel and effective antibiotic entities . Ever since, the prokaryotic cell wall has been considered as a specifically suitable target for antibacterial therapies. − Despite the high clinical relevance of antibiotics targeting peptidoglycan assembly, drug development activities directly resulting in new cell wall synthesis inhibiting entities are still severely hindered today.…”

Section: Introductionmentioning

confidence: 99%

Molecular Imaging of Isolated Escherichia coli DH5α Peptidoglycan Sacculi Identifies the Mechanism of Action of Cell Wall-Inhibiting Antibiotics

et al. 2023

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Antibiotic resistance of pathogenic bacteria needs to be urgently addressed by the development of new antibacterial entities. Although the prokaryotic cell wall comprises a valuable target for this purpose, development of novel cell wall-active antibiotics is mostly missing today. This is mainly caused by hindrances in the assessment of isolated enzymes of the co-dependent murein synthesis machineries, e.g., the elongasome and divisome. We therefore present imaging methodologies to evaluate inhibitors of bacterial cell wall synthesis by high-resolution atomic force microscopy on isolated Escherichia coli murein sacculi. With the ability to elucidate the peptidoglycan ultrastructure of E. coli cells, unprecedented molecular insights into the mechanisms of antibiotics were established. The nanoscopic impairments introduced by ampicillin, amoxicillin, and fosfomycin were not only identified by AFM but readily correlated with their known mechanism of action. These valuable in vitro capabilities will facilitate the identification and evaluation of new antibiotic leads in the future.

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“…Carbapenem, colistin, and tigecycline are considered last-resort antimicrobials for infections caused by multidrug-resistant (MDR) gram-negative bacteria, such as Enterobacterales, Pseudomonas aeruginosa , and Acinetobacter baumannii , which are serious global public health threats (3, 4, 6). tet (X4) and other tet (X) variants, which encode flavin-dependent monooxygenases that catalyze tigecycline degradation, have emerged mainly in Enterobacterales and Acinetobacter species (3).…”

Section: Introductionmentioning

confidence: 99%

Strand-biased circularizing integrative elements spread tmexCD-toprJ gene clusters encoding RND-type multidrug efflux pumps by repeated transpositions

Dao

Yano

Takemura

et al. 2022

Preprint

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Antimicrobial resistance genes (ARGs) are associated with mobile genetic elements (MGEs) that conscript useful genes into the human-microbe and microbe-microbe battlefields. Thus, under intense selective pressure, ARGs have been constantly adapting and evolving, spreading among microbes. tmexCD-toprJ gene clusters, which encode resistance-nodulation-cell division (RND)-type efflux pumps, confer multidrug-resistance to clinically important antimicrobials, including tigecycline. Noteworthily, these gene clusters have emerged in gram-negative bacteria in humans, animals, and the environment worldwide by MGE-mediated transfer. Here we show a hidden MGE, strand-biased circularizing integrative element (SE), that is recently recognized to mediate transpositions of ARGs, associated with the spread of tmexCD-toprJ gene clusters. We identified multidrug-resistant isolates of Aeromonas species in a water environment in Vietnam that harbored multiple copies of tmexCD-toprJ in their chromosomes that were associated with SEs. In particular, Aeromonas hydrophila NUITM-VA1 was found to harbor two copies of a novel variant of tmexC3.3D3.3-topJ1 within cognate SEs, whereas Aeromonas caviae NUITM-VA2 harbored four copies of a novel variant of tmexC2D2.3-topJ2 within cognate SEs. Based on the nature of SE to incorporate a neighboring sequence into the circular form and reinsert it into target sites during transposition, we identified the order of intragenomic movements of tmexCD-toprJ gene clusters. Altogether, our findings suggest that most known subgroups of tmexCD-toprJ and their subvariants underwent transpositions among bacterial chromosomes and plasmids via SEs. Hence, a tmexCD-toprJ gene cluster ancestor may have been initially mobilized via SE, subsequently spreading among bacteria and evolving in new hosts.

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Mobile Tigecycline Resistance: An Emerging Health Catastrophe Requiring Urgent One Health Global Intervention

Cited by 24 publications

References 128 publications

The European Union Summary Report on Antimicrobial Resistance in zoonotic and indicator bacteria from humans, animals and food in 2020/2021

The European Union Summary Report on Antimicrobial Resistance in zoonotic and indicator bacteria from humans, animals and food in 2020/2021

Molecular Imaging of Isolated Escherichia coli DH5α Peptidoglycan Sacculi Identifies the Mechanism of Action of Cell Wall-Inhibiting Antibiotics

Strand-biased circularizing integrative elements spread tmexCD-toprJ gene clusters encoding RND-type multidrug efflux pumps by repeated transpositions

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